What is the schematic diagram of the development of disease complications in Chronic Kidney Disease (CKD) patients?

Schematic Diagram of Disease Complications in CKD Patients

The development of complications in chronic kidney disease (CKD) follows a progressive pattern where multiple complications begin early in the disease course, often at CKD stages 1-2, and worsen as kidney function declines, with cardiovascular disease being the leading cause of morbidity and mortality in these patients. 1

Stages of CKD and Complication Development

CKD Classification Framework

• CKD is defined as kidney damage or GFR <60 mL/min/1.73 m² persisting for >3 months 1
• The disease is classified into 5 stages based on GFR levels 1:
  • Stage 1: Kidney damage with normal or increased GFR (≥90 mL/min/1.73 m²)
  • Stage 2: Kidney damage with mild decrease in GFR (60-89 mL/min/1.73 m²)
  • Stage 3: Moderate decrease in GFR (30-59 mL/min/1.73 m²)
  • Stage 4: Severe decrease in GFR (15-29 mL/min/1.73 m²)
  • Stage 5: Kidney failure (<15 mL/min/1.73 m² or dialysis) 1

Temporal Development of Complications

• Many complications of CKD begin to develop in the earliest stages of disease, long before patients reach end-stage renal disease (ESRD) 1
• These complications include anemia, cardiovascular disease, bone disease, and nutritional problems, representing multiple missed opportunities for intervention 1

Major Complications by System

Cardiovascular Complications

• Left ventricular hypertrophy (LVH) begins early in CKD with approximately 30% of patients with mild renal insufficiency (creatinine clearance 50-75 mL/min) already showing evidence of LVH 1
• LVH prevalence increases steadily as kidney function declines, affecting approximately 75% of patients by the start of hemodialysis therapy 1, 2
• Cardiovascular disease is the leading cause of death in CKD patients, with most patients dying from cardiovascular complications before reaching kidney failure 3
• Arterial disease in CKD is characterized by calcification and vascular stiffness 3

Hematologic Complications

• Anemia prevalence increases markedly as GFR decreases below 60 mL/min/1.73 m² 1
• Anemia reduces oxygen-carrying capacity, leading to tissue hypoxia and contributing to cardiovascular complications 2

Metabolic and Bone Disorders

• Abnormalities in calcium, phosphorus, and bone metabolism begin early in CKD 1
• Hyperphosphatemia becomes more prevalent as GFR decreases 1
• Secondary hyperparathyroidism develops as kidney function declines 4

Nutritional Complications

• Nutritional impairment, evidenced by decreasing albumin levels, becomes significant in patients with GFR <60 mL/min/1.73 m² 1
• Malnutrition contributes to increased morbidity and mortality 1

Neurological Complications

• Neurological changes occur as kidney function declines 1
• Uremic encephalopathy can develop in advanced CKD 4

Multiplicity of Complications

• The likelihood of having multiple abnormalities increases with decreasing GFR 1
• At GFR <30 mL/min/1.73 m², patients commonly present with multiple complications including hypertension, difficulties in ambulation, anemia, hypoalbuminemia, and hyperphosphatemia 1

Risk Factors and Progression Model

• The public health model for CKD identifies risk factors associated with initiation and progression of disease 1

• These include:

  • Susceptibility factors (e.g., age, family history)
  • Initiation factors (e.g., diabetes, hypertension)
  • Progression factors (e.g., poor glycemic control, hypertension)
  • End-stage factors (e.g., low dialysis dose) 1

• Complications of CKD can be addressed through:

  • Primary prevention: targeting those at increased risk
  • Secondary prevention: early detection and treatment of CKD
  • Tertiary prevention: reducing complications in established CKD 1

Intervention Points Along CKD Progression

• Each stage of CKD requires specific interventions 1:

  • Stage 1: Screening, CKD risk reduction
  • Stage 2: Diagnosis and treatment of comorbid conditions, slowing progression, CVD risk reduction
  • Stage 3: Estimating progression
  • Stage 4: Evaluating and treating complications
  • Stage 5: Renal replacement therapy (if uremia present) 1

• Early intervention is critical since many complications begin years before patients present for dialysis 1

• Failure to address issues like cardiovascular disease during progressive CKD results in dialysis patients who already have severe comorbidities 1

Key Clinical Implications

• Screening and early detection of CKD are essential for preventing complications 4
• Management should focus on both slowing CKD progression and treating/preventing complications 4
• Cardiovascular risk reduction is paramount at all stages of CKD 3, 5
• Novel therapies such as SGLT2 inhibitors have shown benefits in reducing cardiovascular complications in CKD patients 3